Efeito do tratamento com lisdexanfetamina no neurodesenvolvimento de ratos e sua repercussão na fase adulta

Abstract

The Attention Deficit Hyperactivity Disorder (ADHD) is among the most common psychiatric disorders of childhood and adolescence, with prevalence rates from 3.5% to 5.6% of the young population, and it is defined as a persistent pattern of inattention and/or hyperactivity-impulsivity, with obvious symptoms before 12 years old. The lisdexamfetamine dimesylate (LDX) is a new psychostimulant used to treat ADHD with promising results, but lack studies to verify their long term effects. Thus, the present study was investigated the effect of treatment with LDX in neurodevelopment and its repercussions in adulthood, assessing changes in behavioral and neurochemical parameters. Wistar male rats were used, with 21 days of born, submitted to Open Field Test and divided into two groups: the experimental group, treated with LDX at doses of 2 mg/kg and 5 mg/kg and the control group, which received saline solution. The drug was administered by gavage over 10 days and the last day of treatment the behavioral testing was performed. 30 days after the treatment period, no experimental procedure, the animals were again evaluated in the Open Field Test, sacrificed and dissected, extracting their brain areas for the realization of neurochemical tests, in which the levels of oxidative stress were measured through determining the concentration of nitrite/nitrate, the production of acid reactive substances to thiobarbituric acid (TBARS) and by analyzing the levels of reduced glutathione (GSH). The results of behavioral and neurochemical studies indicate the increased behavioral activity, increased concentration of nitrite/nitrate or lipid peroxidation and decrease in GSH levels in mice treated with 5 mg/kg LDX in periods after useing the drug, with changes in the concentration of dopamine and persistent oxidative stress in the adult animal, which suggests that pharmacological treatments performed during childhood and adolescence may interfere the brain development and cause repercussions in adulthood of the members.